The present invention provides novel compounds, novel compositions, methods of their use and methods of their manufacture, such compounds generally pharmacologically useful in the treatment of cardiac arrhythmias. The aforementioned pharmacologic activities are useful in the treatment of mammals. More specifically, the compounds of the present invention are orally active Class III antiarrhythmic agents which, by effectively prolonging repolarization of a cardiac cell action potential, can be used effectively to treat certain cardiac arrhythmias. At the present time, there is a need in the area of cardiology therapy for such an agent.
Antiarrhythmic drugs have been grouped together according to the pattern of electrophysiological effects that they produce and/or their presumed mechanisms of action. Thus, Class I antiarrhythmic agents are characterized by being sodium channel blockers, Class II antiarrhythmic agents are beta-adrenergic blockers, Class III antiarrhythmic agents prolong repolarization and Class IV antiarrhythmic agents are calcium channel blockers.
Currently, there are very few Class III antiarrhythmic agents available for therapeutic use. Among them is bretyllium. Bretyllium's usefulness is limited however, and currently its therapeutic use is reserved for life-threatening ventricular arrhythmias that are refractory to therapy. Thus, bretylium's use is generally confined to intensive care units. It is an object of this invention to provide Class III antiarrhythmic agents of broader therapeutic use than existing Class III antiarrhythmic agents. There is a need in the area of cardiovascular therapeutics for an agent which has broader clinical usefulness. The compounds of the present invention meet this need in the art by providing for orally active therapeutic agents for the treatment of cardiac arrhythmias.